This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Holoprosencephaly-spectrum defects can be induced by embryonic exposure to ethanol or Hedgehog signaling antagonists. Our first aim seeks to define the dose- and stage-dependent effects of Hedgehog signaling antagonist exposure through detailed characterization of CNS and craniofacial phenotype in affected fetal specimens. Our second aim is to apply MR microscopy in the study of facial morphometrics. Face shape is known to be useful in predicting both underlying brain morphology as well as predicting predisposition for congenital malformations. We will use MR acquired 3D facial images to identify morphological features of the face that are associated with specific brain malformations and to determine whether facial clefting can be predicted by subtle (non-clefting) morphometric changes. We intend for the first aim described above to be inter-relatable with work already performed in the Sulik laboratory defining the craniofacial and CNS phenotype of fetal mice exposed to ethanol embryonically. Thus, we will use the existing MRM protocol. We anticipate that the second research aim, utilizing MR for facial morphometric analysis, will be best served by modifying this protocol used for Aim1 by the addition of diffusion weighting to optimize the image quality of the facial surface.